Senile dementia caused by such cerebral disorders as cerebrovascular disorder, cerebral circulation disorder, cerebral metabolism disorder and memory disturbance has become a social problem in the society with prolonged life-span. Development of drugs useful for improving mneme, cerebral circulation and cerebral metabolism are thus desired. A recent clinical report [M. F. Mazurek et al., Neurology, 36, 1133(1986)] revealed a remarkable decrease of peptides participating in mneme or neurotransmission in brains of senile dementia patients.
Prolyl endopeptidase is an enzyme degrading peptides containing proline, and inactivates vasopressin, thyrotropin releasing hormone, neurotensin and the like, responsible for mneme and neurotransmission, which has propagated mneme and learning tests on the inhibitors of the enzyme. It is known that a compound inhibiting prolyl endopeptidase has resistance to amnesia (Japanese Patent Unexamined Publication No. 62-201877; Japanese Pharmacological Journal, Minanisato, et al., 89, 323(1987); ibid, Taira, et al., 89, 243(1987)).
Drugs improving cerebral circulation, cerebral vasodilators, cerebral metabolism accelerators, and the like are clinically used as drugs for treating cerebrovascular disorders. These drugs, however, exhibit only insufficient improvement in neurological symptoms or inability of daily life in the patients, even though they are recognized to improve subjective symptoms.
Therefore, a drug has been expected which has an action for improving cerebral circulation and cerebral metabolism in combination with an action for improving neurological disorders, such as resistance to amnesia and the like, and an action for improving disorders of movements in daily life.
Thus, the present inventors have made various investigations for research of a compound having a prolyl endopeptidase inhibitory action and an action of improving cerebral metabolism, and have synthesized an imide derivative of amino acid, having resistance to amnesia. The inventors have submitted a patent application (Japanese Patent Unexamined Publication No. 1-2503070). Further research works have been continued thereafter so as to make intensive investigations to generate a novel drug for improving mneme, cerebral circulation and brain metabolism, which drug has an excellent prolyl endopeptidase inhibitory action in combination with an action for improving cerebral circulation and cerebral metabolism. Thus, the present invention has been achieved.